In recent years there has been increasing interest in improving adhesives and sealants in the field of surgical aids for improving the efficiency of classical sutures or for replacing them partially or totally and thus suppressing the need of using yarns or staples or other invasive suture and tissue repair materials.
Improved adhesives and sealants are also needed for fixing materials such as membranes, meshes, sheets, bandages, prostheses etc. . . onto living soft or hard tissues including e.g. muscles, skin, nerves, tendons, ligaments, blood vessels, bones, cartilages, nails, hair, teeth etc. . . that partially or totally suppress the need for using yarns, staples, screws, pins or other fixing devices that can damage or provoke additional injury to tissues or nerves and provoke pain.
Also improved adhesives and sealants that enable perfect closure when requested and avoid leakage of fluids are needed. The use of adhesive and sealants is also preferred for avoiding excessive deformation of the tissue to be repaired.
Several compositions that are used as adhesive or sealant for tissue adhesion or for fixing materials or devices onto tissues are currently commercially available. Nevertheless, these compositions show relevant drawbacks.
For instance, cyanoacrylate-based products are known for a very long time as efficient surgical glues. Such compositions are highly adhesive, in very short periods of time. Cyanoacrylate adhesive compositions harden very quickly which is a hurdle for its use in the field of tissue repair, or for fixing solid supports onto living material. As a matter of fact, such high strength and fast-hardening glues exclude the removal and further repositioning of the material to be stuck. Moreover neither the biocompatibility nor the non-toxicity have been demonstrated and it has been suspected that the exothermic reaction during the hardening process provokes the release of toxic degradation compounds.
Fibrin sealant products which are based on the polymerization of fibrinogen and thrombin in the presence of growth factor XIII and fibronectin lead to the formation of a fibrin clot which enables sticking.
Proteins, such as collagen and albumin, cross-linked with aldehyde are also already used and commercialized (GRF (Gelatine Resorcine Formaldehyde) glue or French glue). Concern regarding the toxicity of the cross-linking agents used in this technology has frequently been raised. Moreover, the mammalian origin of both collagen and albumin constitutes a major concern for approval onto the market due to pronounced risks of allergenic, immunogenetic or infectious related diseases.
Natural polyphenolic adhesive proteins secreted by organisms such as mussels (Mytilus edulis) as well as their synthetic analogues are capable of adhering to a variety of surfaces under water when cross-linked and thus have also raised interest recently. However the cost-effectiveness and in some cases the use of toxic cross-linkers may compromise such approaches.
Polyethylene glycol (PEG) polymers used for tissue adhesion are also on the market. They need to be mixed and photopolymerized for activating the adhesion (FocalSeal-L, Genzyme Biosurgery, Inc.) which makes them difficult to use. Similar products have been developed that do not require photopolymerization and rely on mixing and reaction of N-hydroxysuccinyl PEG and thiolated PEG powders with acidic aqueous solution (CoSeal®, Angiotech Pharmaceuticals, Inc.). However the preparation is long and the injection of local acid and basic solutions present safety concerns. DuraSeal® (Confluent Surgical, Inc.) is another example of two-part self-curing PEG hydrogel products (PEG ester solution and a trilysine amine solution).
Adhesive compositions comprising chitosan or derivatives thereof have been reported in the art.
For example, Ono K. et al. (Journal of biomedical materials research, 2000, 49, 289-295) describe a chitosan containing both azide and lactose moieties (Az-CH-LA) which is then photocrosslinked by application of an ultra-violet (UV) irradiation resulting in an insoluble hydrogel. The modified chitosan (Az-CH-LA) requires illumination with UV light for generating highly reactive nitrene groups that will react with each other or with amino groups of the chitosan (or tissue proteins) resulting in covalent linkage (chemical cross-links) between molecules or with tissue proteins providing adhesive properties. A composition containing the photochemically cross-linked insoluble hydrogel in water showed adhesive properties comparable to fibrin glues when tested in experiments consisting in testing the adhesion of two pieces of ham together.
In another example, US 2005/0112182 provides a N-alkyl chitosan derivative having an ultra-violet ray-curable functional group capable of forming a polymer upon irradiation with ultra violet rays usable as an adhesive or a film or a covering agent.
Chitosan, chitin and chitin-glucan copolymers are natural polysaccharides of great technological importance, as there are easily available in massive amounts, and as they present unique characteristics often not found for synthetic. Chitin is the main component of insect and crustacean cuticulum, and is also part of the cell walls of fungi and other organisms. Chitin is the linear polymer of N-acetyl-(D)-glucosamine linked through a β(1.4) osidic bond, that can be represented by Formula I.

Chitosan is the random copolymer of N-acetyl-(D)-glucosamine and (D)-glucosamine linked by β(1-4)glucosidic bonds, that can be represented by Formula II. Chitosan is obtained by N-deacetylation of chitin.

Chitin and chitosan polymers may be linked to or associate with glucan.
An important problem of some of the above-mentioned prior art adhesive compositions is however that they do not allow the compositions to be detached and/or repositioned, e.g. onto a living tissue or organ. However, there is a great need for a physician or practitioner to correct, if needed, the position of adhesive compositions or a material coated with such composition without compromising the adhesive strength and without provoking visible damage to the tissue or organ to which the adhesive composition or the material is attached.
Another disadvantage of prior art adhesive compositions is that the compositions often require manipulations such as UV irradiation or the mixing of multiple components for the composition to become adhesive. This is not practical and sometimes even impossible in a surgical setting.
Furthermore, it is not always possible with prior art adhesive compositions to adequately control their adhesive strength. Increasing or changing the adhesive strength of prior art compositions is generally done by increasing the pressure to apply the adhesive composition on a tissue or organ. However, this may cause unwanted damage to such tissues or organs.
In view of the above, there remains a great need in the art for improved adhesive compositions which can overcome at least one or more of the above-indicated problems.